title: Sequence analysis and structure prediction of enoyl-CoA hydratase from Avicennia marina: implication of various amino acid residues on substrate-enzyme interactions.
abstract: Enoyl-CoA hydratase catalyzes the hydration of 2-trans-enoyl-CoA into 3-hydroxyacyl-CoA. The present study focuses on the correlation between the functional and structural aspects of enoyl-CoA hydratase from Avicennia marina. We have used bioinformatics tools to construct and analyze 3D homology models of A. marina enoyl-CoA hydratase (AMECH) bound to different substrates and inhibitors and studied the residues involved in the ligand-enzyme interaction. Structural information obtained from the models was compared with those of the reported crystal structures. We observed that the overall folds were similar; however, AMECH showed few distinct structural changes which include structural variation in the mobile loop, formation and loss of certain interactions between the active site residues and substrates. Some changes were also observed within specific regions of the enzyme. Glu106 is almost completely conserved in sequences of the isomerases/hydratases including AMECH while Glu86 which is the other catalytic residue in most of the isomerases/hydratases is replaced by Gly and shows no interaction with the substrate. Asp114 is located within 4Å distance of the catalytic water which makes it a probable candidate for the second catalytic residue in AMECH. Another prominent feature of AMECH is the presence of structurally distinct mobile loop having a completely different coordination with the hydrophobic binding pocket of acyl portion of the substrate.
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Uzma
authors.initials: U
authors.lastname: Jabeen
authors.forename: Asmat
authors.initials: A
authors.lastname: Salim
mesh_terms: D000595:Amino Acid Sequence; D032407:Avicennia / Q000201:enzymology* / Q000235:genetics; D020134:Catalytic Domain / Q000235:genetics; D018360:Crystallography, X-Ray; D004746:Enoyl-CoA Hydratase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009154:Mutation; D010802:Phylogeny; D010940:Plant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D010940:Plant Proteins; D004746:Enoyl-CoA Hydratase
keywords: AMECH; Avicennia marina enoyl-CoA hydratase; DAC-CoA; ECH; Homology modeling; SPDV; Salt stress; Structure prediction; Substrate interactions; dimethyl amino cinnamoyl-CoA; enoyl-CoA hydratase; swiss PDB viewer